Zydus Lifesciences has announced the conclusion of subject enrolment in the Phase II clinical trial of Usnoflast (ZYIL1) to treat amyotrophic lateral sclerosis (ALS).

The proof-of-concept, randomised, placebo-controlled, multicentre, double-blind study is aimed at assessing twice-a-day oral dose of Usnoflast in patients aged 18 to 80 years.

A total of 24 ALS patients were enrolled across seven study sites in India.

This trial will assess the safety, pharmacokinetics, tolerability, and pharmacodynamics of Usnoflast versus placebo.

The primary endpoint is the variation in the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) score at weeks four, eight, and 12 from baseline.

Secondary endpoints include measuring Slow Vital Capacity (SVC) and neurofilament levels, both significant indicators of ALS progression.

A rare and fatal neurodegenerative disease, ALS leads to an average life expectancy of three to five years post-diagnosis.

An oral NLRP3 inflammasome inhibitor, usnoflast has shown high potency in human whole blood assays and the ability to suppress inflammation caused by the NLRP3 inflammasome.

Pre-clinical studies have demonstrated its efficacy in neuroinflammation, Parkinson’s disease, inflammatory bowel disease, and multiple sclerosis.

The asset was found to be distributed in the brain and CSF in various nonclinical species, including mice, rats, and non-human primates.

With an acceptable ADME profile and a good safety margin, Usnoflast was safe and well-tolerated in Phase I studies.

In addition to the ALS trial, Zydus has initiated a Phase II trial of Usnoflast in ulcerative colitis.

The company has already established Phase II proof-of-concept in cryopyrin-associated periodic syndrome (CAPS) patients.

Previously, the US Food and Drug Administration granted orphan drug designation for Usnoflast to treat CAPS.